Silver derives its broad spectrum antimicrobial activity from the ability of silver ions to bind irreversibly to a variety of nucleophilic groups commonly available in cells of bacteria, viruses, yeast, fungi and protozoa. Binding to cellular components disrupts the normal reproduction and growth cycle resulting in death of the cell. Capitalizing on its potent activity, silver and its compounds have been incorporated over the past several decades in a variety of wound care products such as dressings, hydrogels, hydrocolloids, creams, gels, lotions, catheters, sutures, and bandages.
The preferred form of silver in antimicrobial products has been its compounds or salts as the metallic form of the element itself lacks therapeutically effective oligodynamic action. The compounds or salts upon contact with an aqueous medium ionize to yield silver ions that become available for antimicrobial action. The majority of silver compounds are also photosensitive or heat sensitive making their utilization in stable commercial products challenging. Alternatively, silver metal has been deposited as thin films on antimicrobial catheters and wound dressings by a vacuum sputter process or by electroplating to form an antimicrobial surface. The mechanism of silver metal containing products is thought to involve silver oxide that forms on its surface. After coming in contact with fluids, silver oxide which is weakly soluble in water, releases therapeutically effective amount of silver ions. Because the deposited silver has a small surface area, it releases relatively few ions and therefore can provide only limited antimicrobial activity and effective long term sustained release can be quite difficult. Sustained release activity is required for long term care of patients undergoing procedures such as catheterization and pain management. To some extent, this difficulty can be overcome by increasing the silver loading in the product but this approach leads to an increased risk of cytotoxicity to the mammalian cells and often causes staining of areas contacting the product. Additionally, the manufacture of such devices is also expensive as it involves vacuum sputtering, an operation that requires specialized equipment.
One solution to improving silver ion release from silver metal bearing surfaces without increasing loading is to increase the surface area of available silver on a per unit mass basis. Such an approach would permit very large increase in surface area as the particles sizes approach nanometer range. Recently, several inventors have claimed the production of silver in the form of dry nanoparticles where sizes approach the order of nanometers. The silver nanoparticles allow for very large surfaces per unit mass as surface area per unit volume (or mass) is inversely proportional to its diameter. The large surface area allows for surface oxide layers that in turn improve the silver ion release upon contact with water. Unfortunately, it is known that very fine pure metal particles as powders in dry state are potential fire hazard if exposed to air. Air exposure ignites the particles due to very rapid oxidation reactions that are highly exothermic.
Other processes for silver particles have been based on thermal evaporation of pure metal under vacuum. The processes are energy intensive, require expensive equipment, demand high maintenance and the particles produced require some form of passivation of surfaces to reduce fire and explosion risk. Additional steps such as passivation increase costs and may adversely affect the antimicrobial activity possibly requiring greater amount of silver loading to achieve the minimum inhibitory levels. The dry processes suffer from exposure hazard to the manufacturing personnel as very little is known about the effects of silver nanoparticles in different environments. Further, the silver nanoparticles produced in dry form are present as agglomerates that require re-dispersion, which is an energy intensive process and seldom completely effective.
In summary, neither the dry processes nor wet methods used in known processes offer a simple, inexpensive and non-hazardous method for providing silver nanoparticle compositions that are used to easily render a variety of surfaces antimicrobial.
Therefore, there is a need for antimicrobial compositions comprising silver nanoparticles that can be made by methods that are scalable to high volume manufacturing and utilize chemicals that are relatively non-hazardous. Furthermore the utility of antimicrobial nanoparticles is increased if they are in a form that can be incorporated into compositions or applied directly to surfaces regardless of the shape and contours of devices. Such a form would be in a fluid that is easily dispensed or used as an immersion bath for the devices. Further, such antimicrobial compositions render surfaces treated with them to possess antimicrobial action, including difficult to reach surfaces, such as those of medical devices and do not waste any silver.